Objective: The aim of this study was to confirm the disease causing of a family with hereditary spastic paraplegia. Methods: Detailed clinical characterization analysis was undertake in the HSP family, taking peripheral blood sample from the 9 subjects for the extraction of genomic DNA and the proband underwent next generation sequencing. Potentially causative variants were identified by Sanger sequencing and multiplex ligation-dependent probe amplification. Results: In this study, we obtained clinical and genetic findings in the family with HSP. There were four generations including 47 members, and ten affected members displayed pure HSP, they showed clinical phenotyping that varied in their severity. Gene sequencing suggested that the proband has carried a novel heterozygous variant c.1057_1058insCC in the SPAST gene, and the same mutation was identified in other affected family members.Conclusions: Here, we showed a family with pure autosomal dominant HSP type 4(SPG4). The novel mutation c.1057_1058insCC of SPAST is the causative variant in this HSP-SPG4 family. And the persent study expands the mutation spectrum of SPAST and provides an opportunity to study the genotype-phenotype correlation in SPG4.

Objective: The aim of this study was to confirm the disease causing of a family with hereditary spastic paraplegia. Methods: Detailed clinical characterization analysis was undertake in the HSP family, taking peripheral blood sample from the 9 subjects for the extraction of genomic DNA and the proband underwent next generation sequencing. Potentially causative variants were identified by Sanger sequencing and multiplex ligation-dependent probe amplification. Results: In this study, we obtained clinical and genetic findings in the family with HSP. There were four generations including 47 members, and ten affected members displayed pure HSP, they showed clinical phenotyping that varied in their severity. Gene sequencing suggested that the proband has carried a novel heterozygous variant c.1057_1058insCC in the SPAST gene, and the same mutation was identified in other affected family members.Conclusions: Here, we showed a family with pure autosomal dominant HSP type 4(SPG4). The novel mutation c.1057_1058insCC of SPAST is the causative variant in this HSP-SPG4 family. And the persent study expands the mutation spectrum of SPAST and provides an opportunity to study the genotype-phenotype correlation in SPG4.